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Comment
. 2016 Aug 8;30(2):194-196.
doi: 10.1016/j.ccell.2016.07.010.

Sticking It to Cancer with Molecular Glue for SHP2

Hao Ran  1 , Ryouhei Tsutsumi  1 , Toshiyuki Araki  1 , Benjamin G Neel  2
Affiliations
Comment

Sticking It to Cancer with Molecular Glue for SHP2

Hao Ran et al. Cancer Cell. .

Abstract

Much effort has been expended to develop inhibitors against protein-tyrosine phosphatases (PTPs), nearly all of it unsuccessful. A recent report, describing a highly specific, orally bioavailable inhibitor of the PTP oncoprotein SHP2 with in vivo activity, suggests that allostery might provide a way forward for PTP inhibitor development.

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Figures

Figure 1
Figure 1
Schematics illustrating key features of SHP2 regulation and function. (A) SHP2 switches from a closed (inactive) to an “open” active form upon binding to specific phosphotyrosyl peptide motifs in RTKs/scaffold proteins. (B) Role of SHP2 in growth factor/cytokine-dependent RAS/ERK pathway activation (left) and in mediating the inhibitory function of PD-1 (and other immune-inhibitory receptors) on TCR signaling (right). (C, D) Effects of active site-targeting inhibitor (C) or SHP09 (D) on SHP2.
See this image and copyright information in PMC

Comment on

  • Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases.
    Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, Dobson JR, Deng Z, Fei F, Firestone B, Fodor M, Fridrich C, Gao H, Grunenfelder D, Hao HX, Jacob J, Ho S, Hsiao K, Kang ZB, Karki R, Kato M, Larrow J, La Bonte LR, Lenoir F, Liu G, Liu S, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Price E, Quinn C, Shakya S, Shultz MD, Slisz J, Venkatesan K, Wang P, Warmuth M, Williams S, Yang G, Yuan J, Zhang JH, Zhu P, Ramsey T, Keen NJ, Sellers WR, Stams T, Fortin PD. Chen YN, et al. Nature. 2016 Jul 7;535(7610):148-52. doi: 10.1038/nature18621. Epub 2016 Jun 29. Nature. 2016. PMID: 27362227

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